Plant-based medicines or drugs are of ancient origin and their use is known in cultures throughout the world. A common concern with herbal medicine is that herbs are slow acting in treating an ailment. Therefore, a movement to identify individual active ingredients in beneficial plants developed in the 18th century, leading into a transitional period from the use of plant-based products to the use of pharmaceutical drugs such as extracts and purified chemicals, sometimes referred to as allopathic drugs, which act comparatively quickly.
Many active herbal compounds have been extracted and chemically synthesized for use in the modern allopathic medical practice. For example, Indian snake root, also known as Rauwolfia serpentina, has been used in Indian ayurvedic medicine for centuries to cure anxiety, headaches, and high blood pressure. In 1947, the alkaloid, reserpine, was extracted from snake root and used in the treatment of hypertension.
Similarly, the roots of the medicinal plant Withania somnifera (L.) Dunal have been used in the Ayurvedic tradition of India as it possesses a variety of activities including anti-inflammatory (Anbalagan, et al. (1981) Indian J. Exp. Biol. 19:245-249), immunomodulatory (Ziauddin, et al. (1996) J. Ethnopharmacol. 50:69-76; Dhuley, et al. (1997) J. Ethnopharmacol. 58:15-20), cardioprotective (Dhuley, et al. (2000) J. Ethnopharmacol. 70:57-63), antioxidant (Dhuley, et al. (1998) J. Ethnopharmacol. 60:173-178), and antiproliferative (Jayaprakasam, et al. (2003) Life Sci. 74:125-132) activities. The primary bioactive constitutents of W. somnifera are known as withanolides. These compounds are structurally diverse steroidal compounds with an ergosterol skeleton in which C-22 and C-26 are oxidized to form a δ-lactone (Ray, et al. (1994) Prog. Chem. Org. Nat. Prod. 63:1-106). Withaferin A, the first member of this group, was isolated from W. somnifera in 1965 (Lavie, et al. (1965) J. Org. Chem. 30:1774-1776).

Withaferin A and related withanolides has been proposed to inhibit the actions of many targets including the actin bundling protein annexin II (Falsey, et al. (2006) Nat. Chem. Biol. 2:33-38), the 20S proteasome (Yang, et al. (2007) Mol. Pharmacol. 71:426-437), the intermediate filament protein vimentin (Bargagna-Mohan, et al. (2007) Chem. Biol. 14:623-634), the transcription factor NFκB (Srinivasan, et al. (2007) Cancer Res. 67:246-253), protein kinase C (Sen, et al. (2007) Cell Death Differ. 14:358-367), and the Par-4-dependent apoptosis pathway (Kaileh, et al. (2007) J. Biol. Chem. 282:4253-4264). Given its various activities, various withaferin analogs have been described. See US 2009/0088412; U.S. Pat. No. 7,282,593; WO 2010/030395; and WO 2010/053655.
An increasing number of people are gaining awareness of the advantages of natural products together with a concern over the disadvantages of modern purified drugs. Consequently, there has been an increasing public interest in the identification of new natural products.
Physalis longifolia is a plant native to Kansas. Physalis longifolia, or longleaf groundcherry, occurs throughout the continental United States and into southern Canada. It has a characteristic husked fruit, like tomatillos and the cultivated garden plant known as Chinese lantern, which is in the same genus. These plants are part of the nightshade family, Solanaceae, which includes tomatoes, potatoes, and tobacco. Physalis longifolia fruit was used as a food source by southwestern Native American tribes, including the Zuni and other Puebloan people. It has now been found that this plant contains a withanolide similar in structure to withaferin A.